Organ or tissue failure remains a frequent, costly, and serious problem in health care despite advances in medical technology. Available treatments include organ transplantation, surgical reconstruction, mechanical devices (e.g. pace makers and kidney dialysis machines), drug therapy, and tissue engineering. These treatments, however, are not perfect solutions. Organ transplantation is limited by the availability of donors and complications such as tissue rejection. Surgical reconstruction is costly, highly invasive, and not always effective. Mechanical devices cannot functionally replace an organ, for example, dialysis machines can only help to remove some of the metabolic waste from the body. Likewise, maintaining drug concentration levels in vivo, comparable to the control systems of the body, are difficult to achieve. Finally, tissue engineering while promising, is encumbered by size limitations that typically require the assembly of the engineered tissue in vitro, followed by surgical implantation in vivo.
Recent advances in the medical, biological and physical sciences have given rise to new strategies for tissue engineering. For example, in one approach to engineering artificial skin, dermal fibroblasts are suspended in a polymer mesh, whereas another approach involves fibroblasts seeded in a collagen gel, which is then coated with a layer of human epidermal cells (see, e.g., Vogel, et al., Ann. Rev. Biomed. Eng. 5:441-463 (2003)). The use of extracellular matrix (ECM) molecules, such as collagen, is an area of active research in tissue engineering as a way to facilitate the regeneration or repair of damaged tissue in vivo.
Although many different compounds and cellular constituents are important for repair and regeneration of injured tissue, the ECM is of particular interest. ECM proteins play a pivotal role in cell adhesion, cell signaling, cell proliferation, and regulating tissue organization and differentiation. The main components of the ECM include structural proteins such as collagen and elastin, adhesive proteins such as laminin, fibronectin, and collagen IV, anti-adhesive proteins such as tenascin, thrombospondin, and osteopontin, and proteoglycans (see, e.g., Corda, et al., Heart Failure Reviews 5:119-130 (2000)). ECM molecules also have the ability to activate various intracellular signaling pathways, depending on the nature of the adhesion complex formed between the cell and the ECM protein. (see, e.g., Vogel, et al., Ann Rev. Biomed. Eng. 5:441-463 (2003).
Cells adhere to and interact with the ECM via specific receptors. One class of such receptors is the integrin proteins, which make up a large family of transmembrane heterodimer receptors composed of alpha and beta subunits. There are at least fourteen known alpha subunits and eight known beta subunits that associate in various combinations to form at least twenty distinct receptors. One class of integrin receptors known to interact with ECM proteins are integrins having the β1 subunit, also known as very late antigen (VLA) proteins. VLA proteins are expressed on a variety of cells and serve as receptors for many ECM proteins including collagen, fibronectin, and laminin. Binding of ECM proteins by their cognate receptor (e.g. integrin receptors) is important for both promoting stable interactions between the cells and their environment, and initiating intracellular signaling pathways for a variety of cellular processes important for tissue repair and/or regeneration. For example, ECM-integrin signaling has been shown to play a role in cell migration, cell survival, cellular proliferation, and cellular differentiation. See, Vogel et al. (2003).
The present invention fulfills a need in the area of tissue repair and regeneration that is not currently provided for in the art. In particular, the present invention provides for compositions and methods useful for the repair and regeneration of injured tissues in vivo by targeting an extracellular matrix derived (EMD) peptide to an injured tissue where the EMD peptide can provide a surface for cell attachment and growth, thereby facilitating the repair and regeneration of the injured tissue.